The effects of salicylate on ketogenesis, gluconeogenesis and urea production in rat liver perfusion.
In order to elucidate the relation between the hepatotoxicity of salicylate (SA) and the pathogenesis of Reye's syndrome (RS), urea production, gluconeogenesis and ketogenesis were investigated in isolated perfused rat livers in the presence of salicylate (SA) and oleate. Although urea formation from 0.5 mM NH4Cl, 2 mM ornithine and 0.3 mM oleate was not inhibited by infusion of SA, 3 mM SA caused a 26% decrease of ketogenesis, 85% decrease of 3-hydroxybutyrate/acetoacetate ratio (30HB/AcAc) and 45% increase of oxygen consumption. Glucose production from 2 mM pyruvate in the presence of 0.3 mM oleate decreased by 33% after administration of 3 mM SA, and 30HB/AcAc ratio also decreased by 33%. The decrement of gluconeogenesis and that of the 30HB/AcAc ratio were very close. These results suggested that ATP production was maintained but that the intra-mitochondrial redox state was changed to a more oxidized state after SA administration in perfused rat livers. This change in redox state could be responsible for the decrease of gluconeogenesis. Metabolic characteristics found in RS were not obtained by infusion of 3 mM SA and 0.3 mM oleate in rat livers. Therefore, some other factors in addition to SA seem necessary to establish an animal model of RS.
Terada
N
N
Department of Pediatrics, Kyoto Prefectural University of Medicine, Japan.
Kizaki
Z
Z
Inoue
F
F
Kodo
N
N
Ochi
M
M
Furukawa
N
N
Kinugasa
A
A
Sawada
T
T
D000818:Animals; D005947:Glucose / Q000378:metabolism*; D007659:Ketones / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012202:Reye Syndrome / Q000209:etiology / Q000378:metabolism; D012459:Salicylates / Q000009:adverse effects / Q000494:pharmacology*; D014508:Urea / Q000378:metabolism*
D007659:Ketones; D009829:Oleic Acids; D012459:Salicylates; D019301:Oleic Acid; D014508:Urea; D005947:Glucose